This application is a competing continuation of a Research Scientist Development Award (RSDA) to Charles P. France, currently a Professor of Pharmacology and Experimental Therapeutics and Neuroscience at Louisiana State University (LSU) Medial Center in New Orleans. The overall objectives of research in the candidate's laboratory are to develop reliable drug discrimination procedures for studying drug dependence and withdrawal in non-human species, to use those procedures to examine the dependence potential and the therapeutic potential of a wide range of drugs, and to integrate these behavioral findings with other clinically-relevant measures of drug action. These studies also focus on the receptor mechanisms that mediate the abuse-related effects of drugs by structuring experiments around testable hypotheses that are founded in and guided by receptor theory. This combined approach, whereby behavioral procedures are used in concert with receptor theory, provides a bridge from molecular science to the clinic. During the initial period of support the breadth of research in the candidate's laboratory increased markedly to include studies on: benzodiazepine dependence and withdrawal; self- administration procedures in rats and monkeys; the effects of contingent and non-contingent cocaine administration on cognitive function (learning and memory) and on the hypothalamic-pituitary-adrenal (HPA) axis; as well as endocrine and immune responses to acute and chronic drug treatment. The specific aims in this competing renewal are to evaluate opioids and GABAA modulators (e.g. benzodiazepines) for physical dependence potential, abuse liability and toxicity using drug discrimination, ventilation, antinociception, self-administration, and repeated acquisition procedures as well as schedule-controlled behavior and measures of immune and endocrine function. To augment ongoing and future behavioral studies on efficacy, the candidate plans to initiate a binding assay that is sensitive to variations in efficacy (GTPgammaS binding). Renewal of the RSDA will relieve the candidate of otherwise substantial teaching and administrative responsibilities and, thereby, allow him to fully participate in the research projects that have been initiated during the current period of support, collaborate extensively with other NIH-supported investigators at LSU Medical Center, and spend time training young scientists in his laboratory.